The free energy landscape of the oncogene protein E7 of human papillomavirus type 16 reveals a complex interplay between ordered and disordered regions.

When present, structural disorder makes it very challenging to characterise the conformational properties of proteins. This is particularly the case of proteins, such as the oncogene protein E7 of human papillomavirus type 16, which contain both ordered and disordered domains, and that can populate monomeric and oligomeric states under physiological conditions. Nuclear magnetic resonance (NMR) spectroscopy is emerging as a powerful method to study these complex systems, most notably in combination with molecular dynamics simulations. Here we use NMR chemical shifts and residual dipolar couplings as structural restraints in replica-averaged molecular dynamics simulations to determine the free energy landscape of E7. This landscape reveals a complex interplay between a folded but highly dynamical C-terminal domain and a disordered N-terminal domain that forms transient secondary and tertiary structures, as well as an equilibrium between a high-populated (98%) dimeric state and a low-populated (2%) monomeric state. These results provide compelling evidence of the complex conformational heterogeneity associated with the behaviour and interactions of this disordered protein associated with disease.University of Florence (Italy) “Science without borders” of the Brazilian Ministry of Science and Technology (CNPq

List of species of spiders (Arachnida, Araneae) from the Pico da Neblina, state of Amazonas, Brazil

We present a list of species of spiders collected at the Pico da Neblina, the highest mountain in Brazil (Amazonas, Brazil). We sampled at six altitudes (100, 400, 860, 1,550, 2,000 and 2,400 m a.s.l.), through manual active search, during the night and with a beating tray, during the day. We obtained a total of 3,143 adult individuals, which were assigned to 529 species, from 39 families. The most species rich families were Theridiidae (108 species), Araneidae (98 species) and Salticidae (60 species). Most species were rarely collected, as 389 (73% of total richness) species were represented by up to five individuals, and 197 (37% of total richness) of them by just one individual. We briefly compare our results with those from other spider surveys in the Amazon basin

Terapia a laser de baixa intensidade e Calendula officinalis no reparo de úlcera em pé diabético

OBJETIVO Evaluar los efectos de la Terapia con Láser de Baja Intensidad aislada y asociada con el aceite de Calendula officinalis en la reparación de úlceras en pie diabético. MÉTODO Estudio de caso clínico, experimental, controlado, randomizado, prospectivo, intervencionista, de carácter cuantitativo. La muestra estuvo compuesta de 32 pacientes diabéticos, de ambos géneros. Los participantes fueron distribuidos aleatoriamente en cuatro grupos. Ecografía Doppler, evaluación del Índice Tobillo-Brazo, Inventario breve de dolor y escala visual analógica fueron realizados al inicio y después de 30 días. RESULTADOS Hubo reducción del dolor en los grupos Terapia con Láser de Baja Intensidad y Terapia con Láser de Baja intensidad asociada con los Ácidos Grasos Esenciales, con pOBJECTIVE To evaluate the effects of low-level laser therapy isolated and associated with Calendula officinalis oil in treating diabetic foot ulcers. METHOD An experimental, randomized, controlled, prospective, interventional clinical case study using a quantitative approach. The sample consisted of 32 diabetic patients of both genders. Participants were randomly divided into four groups. Doppler Ultrasound evaluation of the Ankle-Brachial Index, brief pain inventory and analog pain scale were performed at baseline and after 30 days. RESULTS Reduced pain was observed in the Low-level laser therapy and Low-level laser therapy associated with Essential Fatty Acids groups (pOBJETIVO Avaliar os efeitos da Terapia a Laser de Baixa Intensidade isolada e associada ao óleo de Calendula officinalis no reparo de úlceras em pé diabético. MÉTODO Estudo de caso clínico, experimental, controlado, randomizado, prospectivo, intervencional, de caráter quantitativo. A amostra foi composta de 32 pacientes diabéticos, de ambos os gêneros. Os participantes foram distribuídos aleatoriamente em quatro grupos. Ultrassom Doppler, avaliação do Índice Tornozelo-Braquial, Inventário breve de dor e escala de dor analógica foram realizados no início e após 30 dias. RESULTADOS Houve redução da dor nos grupos Terapia a Laser de Baixa Intensidade e Terapia a Laser de Baixa intensidade associada aos Ácidos Graxos Essenciais, com

Shifts between gelatinous and crustacean plankton in a coastal upwellin region

proyectos RADIALES (IEO) y EURO-BASIN (Ref. 264933, 7FP)Variability in the dominance of copepods vs. gelatinous plankton was analysed using monthly time-series covering the last 55 years and related to changes in climatic, oceanographic, and fishery conditions in the upwelling region of Galicia (NW Spain). Seasonality was generally the main component of variability in all groups, both along the coast and in the nearby ocean, but no common long-term trend was found. Coastal copepods increased since the early 1990s, and gelatinous plankton increased in the ocean during the 1980s. Different trends were found for gelatinous plankton in two coastal sites, characterized by increases in either medusae or tunicates. In all series, multiyear periods of relative dominance of gelatinous vs. copepod plankton were evident. In general, copepod periods were observed in positive phases of the main modes of regional climatic variability. Conversely, gelatinous periods occurred during negative climatic phases. However, the low correlations between gelatinous plankton and climatic, oceanographic, or fishery variables suggest that local factors play a major role in their proliferations.7FP, IEOPreprin

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

A PTHi pode prever as variações do cálcio após tiroidectomia total?

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that leads to lower natural reproductive potential and presents a challenge for assisted reproductive medicine because patients may exhibit immature oocyte retrieval and a higher risk of ovarian hyper stimulation syndrome during in vitro fertilization (IVF) treatment. This study aimed to identify potential lipid biomarkers for women with PCOS and a hyper response to controlled ovarian stimulation. Follicular fluid samples were collected from patients who underwent IVF, including normal responder women who became pregnant (control group, n = 11), women with PCOS and a hyper response to gonadotropins (PCOS group, n = 7) and women with only hyper response to gonadotropins (HR group, n = 7). A lipidomic analysis was performed by electrospray ionization mass spectrometry, and candidate biomarkers were analyzed by tandem mass spectrometry experiment. The lipid profiles indicated particularities related to differences in phosphatidylcholine (PCOS and HR), phosphatidylserine, phosphatydilinositol and phosphatidylglycerol (control), sphingolipids (PCOS) and phosphatidylethanolamine (control and HR). These findings contribute to the understanding of the molecular mechanisms associated with lipid metabolism in the PCOS-related hyper response, and strongly suggest that these lipids may be useful as biomarkers, leading to the development of more individualized treatment for pregnancy outcome.Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that leads to lower natural reproductive potential and presents a challenge for assisted reproductive medicine because patients may exhibit immature oocyte retrieval and a higher risk of324554CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2012/06389-4]sem informação2012/06389-4This work was supported by CNPq (National Council for Scientific and Technological Development), Brazil and by grant 2012/06389-4, São Paulo Research Foundation (FAPESP